Buch-Larsen Kristian, Gillberg Linn, Ahmed Haboon Ismail, Marstrand Simone Diedrichsen, Andersson Michael, van Hall Gerrit, Brøns Charlotte, Schwarz Peter
Department of Endocrinology and Metabolism, Diabetes and Bone-metabolic Research Unit, Rigshospitalet, Copenhagen, Denmark.
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nutrition. 2024 Jun;122:112394. doi: 10.1016/j.nut.2024.112394. Epub 2024 Feb 10.
Breast cancer survivors are a growing population due to improved treatment. It is known that postmenopausal women treated for breast cancer may experience weight gain and increased insulin resistance, but detailed knowledge on how chemotherapy impact metabolic and endocrine mechanisms remain unknown.
We performed a thorough, preliminary study to elucidate the differing mechanisms of postprandial absorption and metabolism in postmenopausal early breast cancer (EBC) patients treated with adjuvant chemotherapy compared to healthy controls. We hypothesize that chemotherapy has a negative impact on metabolism in EBC patients.
We examined four postmenopausal women shortly after treatment with chemotherapy for EBC and four age-matched healthy women who served as controls using isotopic tracers during a mixed meal-test. Blood was sampled during the 240 min meal-test to examine postprandial absorption and endogenous synthesis of lipid and carbohydrate metabolites.
We found that insulin concentrations were numerically higher before the meal-test in the EBC patients compared to controls (76.3 pmol/L vs 37.0 pmol/L; P = 0.06). Glucose kinetics was increased postprandial (most pronounced at 30 min, 9.46 mmol/L vs 7.33 mmol/L; P = 0.51), with no difference between the groups regarding liver glucose output. Fatty acid kinetics showed a numeric increase in oleic acid rate of appearance in BC patients, but only during the first hour after the mixed meal. There was no significant difference in VLDL-TAG synthesis between the two groups.
This preliminary study is unique in using advanced tracer methods to investigate in vivo metabolism of EBC patients after chemotherapy although no statistical differences in glucose and fatty acid kinetics was seen compared to controls. However, during the first two postprandial hours, oral glucose and oleic acid appearance in the systematic circulation was elevated in the EBC patients. This could be due to changes in gastrointestinal uptake and further studies with altered set-up could provide valuable insights.
由于治疗手段的改进，乳腺癌幸存者的数量正在不断增加。已知接受乳腺癌治疗的绝经后女性可能会出现体重增加和胰岛素抵抗增加的情况，但关于化疗如何影响代谢和内分泌机制的详细知识仍然未知。
我们进行了一项全面的初步研究，以阐明与健康对照组相比，接受辅助化疗的绝经后早期乳腺癌（EBC）患者餐后吸收和代谢的不同机制。我们假设化疗对EBC患者的代谢有负面影响。
我们在混合餐试验期间，使用同位素示踪剂检查了4名接受EBC化疗后不久的绝经后女性和4名年龄匹配的健康女性作为对照。在240分钟的餐试验期间采集血液，以检查餐后脂质和碳水化合物代谢物的吸收和内源性合成。
我们发现，与对照组相比，EBC患者在餐试验前胰岛素浓度在数值上更高（76.3 pmol/L对37.0 pmol/L；P = 0.06）。餐后葡萄糖动力学增加（在30分钟时最为明显，9.46 mmol/L对7.33 mmol/L；P = 0.51），两组之间肝脏葡萄糖输出没有差异。脂肪酸动力学显示，BC患者油酸出现率在数值上有所增加，但仅在混合餐后的第一小时内。两组之间极低密度脂蛋白-甘油三酯合成没有显著差异。
这项初步研究独特之处在于使用先进的示踪方法来研究化疗后EBC患者的体内代谢，尽管与对照组相比，在葡萄糖和脂肪酸动力学方面没有观察到统计学差异。然而，在餐后的前两个小时内，EBC患者全身循环中口服葡萄糖和油酸的出现有所增加。这可能是由于胃肠道吸收的变化，改变设置的进一步研究可能会提供有价值的见解。
